The PI is a well-established junior investigator in the field of environmental fluid mechanics and transport processes, but now seeks to make a career transition to biomedical applications. The PI's interest in this field developed from preliminary work on biological transport processes in environmental systems, which led to the realization that there has been little study of the fundamental effects of physical transport on the transmission and survival of pathogenic microorgansims. In biofilm-based infections, the presence of low-transport microenvironments is expected to protect pathogens from hazards such as anti-microbial agents. Similar processes are also expected to mediate the survival of pathogens in environmental systems, and thus to play an important role in the transmission of water-borne disease. The PI proposes an extensive training and research program that will prepare him to address fundamental problems in microbiology and biomedicine while also advancing basic knowledge of the role of the physical transport environment in mediating the growth, transmission, and survival of pathogenic microorganisms. The training phase will involve coursework, clinical experience, and instruction in methods for biofilm research. Collaborative research will focus on the development of transport-limited microenvironments within biofilms and the role of these processes in mediating the transmission and survival of the representative pathogenic microorganisms P. aeruginosa and L. pneumophila in biofilms. Laboratory experiments will be used to directly observe transport rates in biofilms, determine pathogen survival when exposed to anti-microbial agents under different transport conditions, and assess the development of antibiotic resistance in pathogens residing in low-transport regions of biofilms. Quantitative analysis (modeling) will be used to assess the fundamental role of physical transport in mediating biofilm processes, and to improve analysis of the risk of water-borne disease transmission.